Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation (Nat Med, 2010, 16:897-902)

報告日期: 2010/09/21
報告時間: 17:10/18:00
報告學生: 莊詠鈞
講評老師: 楊倍昌

Full Text:

Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation

Francesca Fallarino, et al.

Nat Med. 16(8):897-902. (2010)


StudentYung-Chun Chuang

CommentatorProf. Bei-Chang Yang

Time2010/09/21  5:00 P.M.

PlaceRoom 602



  Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that causes myelin sheath damage. Interferon-g is the major treatment for MS. However, this treatment is not always effective (1). High levels of excitatory neurotransmitter glutamate are found in the brains of MS patients (2). However, the link between glutamate and immunopathology is unclear. In this study, the authors found metabotropic glutamate receptor-4 (mGluR4) were participated in the regulation of immune response in a mouse MS model, experimental autoimmune encephalomyelitis (EAE). The mGluR4 deficient (Grm4-/-) and heterozygotes mice (Grm4+/-) progressed to more severe EAE after myelin oligodendrocyte glycoprotein (MOG) immunization. In addition, Th17 cells were increased whereas Treg cells were reduced significantly in mGluR4 deficient mice. Dendritic cells from mGluR4-/- mice but not wild-type mice secreted high levels of IL-6 and low levels of IL-27, which favored the differentiation of Th17 rather than Treg cells. Administration of mGluR4 enhancer could decrease Th17 and increase Treg cells and increase EAE resistance in wild type mice. Thus, this study indicated high amount of glutamate in MS might reflect a protective mechanism in nature and mGluR4 agonist may become a new therapeutic drug for MS patients.



1. Axtell RC, de Jong BA, Boniface K, van der Voort LF, Bhat R, De Sarno P, Naves R, Han M, Zhong F, Castellanos JG, Mair R, Christakos A, Kolkowitz I, Katz L, Killestein J, Polman CH, de Waal Malefyt R, Steinman L, Raman C. 2010. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med 16: 406-12

2. Tracey KJ. 2009. Reflex control of immunity. Nat Rev Immunol 9: 418-28